多黏菌素E治疗严重烧伤后多药耐药革兰阴性杆菌感染的临床评估

Clinical assessment of colistin in treating infections caused by multidrug-resistant gram-negative bacillus in patients with severe burn

目的评估多黏菌素E治疗严重烧伤患者多药耐药（MDR）革兰阴性杆菌感染的疗效及不良反应，为临床合理应用该抗生素提供依据。方法选择笔者单位2005年8月-2009年1月收治的9例MDR革兰阴性杆菌感染烧伤患者，在药物敏感试验显示该感染菌种仅对多黏菌素E敏感或其他抗生素对其无效的前提下，采用多黏菌素E静脉滴注（100×10^4～150×10^4U／d）或静脉滴注联合呼吸道雾化吸入或灌洗（50×10^4～100×10^4U／d）给药。观察其细菌学疗效、临床疗效和不良反应（包括神经毒性和肾毒性，后者比较用药前后血清肌酐、尿素氮和胱抑素C水平）。结果9例患者中，7例为血流和肺部感染，1例血流、肺部和创面侵袭性感染，1例血流和尿路感染。病原菌主要为铜绿假单胞菌、鲍氏不动杆菌和嗜麦芽窄食单胞菌。9例患者应用多黏菌素E治疗后，血液中细菌清除率达92．3％；7例合并肺部感染患者，痰液MDR革兰阴性杆菌检出率从用药前的58．2％降至用药后的14．6％（P〈0．01）；1例合并尿路感染患者尿液中MDR革兰阴性杆菌得以清除。用药后，8例患者被判断为临床有效、1例为临床无效，有效率达88．9％。与用药前比较，9例患者用药后血清肌酐和尿素氮水平呈下降趋势；8例患者血清胱抑素C水平相近（P〉0．05），1例患者明显升高但停药1个月后回降。用药期间和停药5d内患者均未见神经毒性反应或其他不良反应。结论在未出现更有效药物的前提下，合理应用多黏菌素E是目前治疗严重烧伤MDR革兰阴性杆菌感染的良好选择。

Objective To investigate the therapeutic effect and side effects of colistin in treating infections caused by multidrug-resistant （MDR） gram-negative bacillus in patients with severe burn in order to provide the basis for reasonable application of this antibiotic in clinic. Methods Nine burn patients suffered from infections caused by MDR gram-negative bacillus admitted to our institute from August 2005 to January 2009 were involved in this study. On the premises that isolated bacteria were only sensitive to colistin or not sensitive to other antibiotics, patients were treated with intravenous drip of colistin （ 100 × 10^4 - 150 × 10^4U/d） , or intravenous drip combined with administration of the drug into respiratory tract by atomization or instillation （50 × 10^4 - 100 × 10^4 U/d）. The bacteriologic and therapeutic effects and side effects （including neurotoxicity and nephrotoxicity, rise in serum levels of creatinine, urea nitrogen and cystatin C were detected and compared before and after administration） of colistin were observed. Results Out of 9 patients, 7 patients were with bloodstream and pulmonary infections, 1 patient was with bloodstream, pulmonary, and invasive wound infections, and 1 patient was with bloodstream and urinary tract infections. The pathogenic bacteria were proved to be Pseudomonas aeruginosa , Acinetobacter baumannii and Pseudomonas maltophilia. After the administration of colistin, bacteria clearance rate of blood reached 92.3% in 9 patients; isolation rate of MDR gram-negative bacillus of sputum was significantly decreased in 7 patients with pulmonary infection （before treatment 58.2% v.s. after treatment 14.6% , P 〈 0.01 ） ; a complete MDR gram-negative bacillus clearance of urine was observed in 1 patient with urinary tract infection. Colitin was clinically effective in 8 patients but ineffective in 1 patient （effective rate 88.9% ）. Compared with those be： fore administration, serum levels of creatinine and urea nitrogen were decreased after administration in all patients ; no significant difference in serum level of cystatin C among 8 patients was detected, except an obvious elevation in serum level of cystatin C in 1 patient after colistin therapy, and it lowered 1 month after discontinuation. No neurotoxicity or other side effect was observed during medication and 5 days after discontinuation in all patients. Conclusions Reasonable application of colistin is a good option for treating infections caused by MDR gram-negative bacillus in patients with severe burn, as no other more effective drug is found.